This invention is in the field of hemodialysis and peritoneal dialysis and relates to improved materials and procedures for the preparation of dialysates (which are also known as "dialysis solutions" and as "dialysate solutions") comprising bicarbonate ions. The improved materials and improved methods of this invention are applicable to batch preparation of a dialysis solution and to the preparation of a dialysis solution on a continuous basis to supply a single hemodialysis machine which is also known as an "artificial kidney" (sometimes shortened to "kidney"), or to supply a plurality of such machines ("kidneys").
Patent art in the dialysis field is directed mainly towards apparatus and methods of handling dialysate solutions comprising sodium acetate as the primary alkalizing agent. The widespread use of acetate systems came about in the early 1960's when sodium acetate was commonly substituted for sodium bicarbonate as the fixed base in dialysis solutions (See Mion et al, "Substitution of Sodium Acetate for Sodium Bicarbonate in the Bath for Hemodialysis", Trans. Am. Soc. Artif. Internal Organs, 10:110, 1964).
This was done primarily because the sodium acetate-containing solutions were more stable in use in that the acetate ion does not cause calcium and magnesium ions to precipitate, whereas the available sodium bicarbonate-comprising solutions were less stable because of the low solubility of calcium and magnesium carbonates which tended to precipitate, thereby changing the ion concentration of the dialysis solution and tended to plug the semiporous membranes comprising the artificial kidney. The tendency for calcium and magnesium carbonates to precipitate at solution use concentrations caused the switch in about 1964 from sodium bicarbonate to sodium acetate as the primary alkalizing agent. This switch also made possible the use of proportioning pumps to handle dialysis solution concentrates (which, on dilution, form dialysis solutions).
Information indicating that there is "less dialysis-induced moribidity and vascular instability with bicarbonate in dialysate" is now surfacing (See, for example, Graefe et al, March, 1978 Annals of Internal Medicine, Vol. 88, No. 3 at pages 332-336). It is now apparent that bicarbonate dialysate solutions, rather than acetate solutions, are better tolerated by patients.
Prior art systems wherein dialysis solutions are prepared by admixing an acid-comprising concentrate and a bicarbonate-comprising concentrate with water are known. One such system is described in U.S. Pat. No. 4,202,760 (Storey et al). Another system is known as the Bio-Systems MAKS 400 Bicarbonate Supply Machine. Still another is known as the Drake-Willock Central Delivery System 7702. These systems are designed to use commercially available state-of-the-art acid comprising concentrates and bicarbonate-comprising concentrates as hereinafter described. It is recognized that products of this invention can be adapted for use in these systems provided specific equipment modifications and procedures are followed as hereinafter described.
The apparatus of the Storey et al patent comprises a main supply line between a water supply and the "kidney", and includes a primary recirculation loop including venturi means for mixing the dialysate concentrate with de-aerated water and, optionally, a secondary recirculation loop for preliminarily forming a dilute bicarbonate containing solution which is then fed to the primary recirculation loop for mixing with the dialysate components and supply to the "kidney". The Storey et al invention requires recirculation of a quantity of the mixed fluid through the mixing venturi in both recirculating loops in an amount which exceeds the fresh water input rate by an amount of preferably 50 to 150 percent of the fresh water intake. The preferred operating method includes the bicarbonate addition step as a partial or complete replacement for acetate in the produced hemodialysis solution.
In one example of the Storey et al patent as set forth to illustrate the best form of the invention contemplated for use in hemodialysis where all of the acetate in a normal dialysate is replaced by bicarbonate, the bicarbonate-saline concentrate of Storey et al is a mixture of 31.4 grams per liter (g/l) of NaCl and 60.6 g/l of NaHCO.sub.3, and a modified dialysate acid concentrate containing 160 g/l NaCl, 5.5 g/l KCl, 8.2 g/l CaCl.sub.2, 5.6 g/l MgCl.sub.2 and 5.1 g/l HCl. As taught by Storey et al, the uniqueness of their apparatus for preparing dialysate for use in hemodialysis resides in the use of recirculating in-line material through a venturi used as a means to introduce concentrated solutions into the recirculating material.
The Bio-Systems MAKS 400 Bicarbonate Supply Machine comprises: (a) an acid-comprising concentrate measuring tank; (b) a bicarbonate-comprising concentrate measuring tank; (c) a solution mixing tank; (d) a water supply; (e) a dialysate supply holding tank; (f) various means for temperature control and material handling. The MAKS 400 Bicarbonate Supply Machine is designed to utilize state-of-the-art acid-comprising concentrates and bicarbonate-comprising concentrates by admixing said concentrates with water in a time sequence controlled batch manner such that, when approximately one volume of acid concentrate and two volumes of bicarbonate concentrate are mixed with water, 35 volumes of dialysate is produced.
Commercially available products, such as Naturalyte #9006, may be used in this machine. The acid concentrate of Naturalyte #9006 contains 7.149 g/l CaCl.sub.2, 0.876 g/l MgCl.sub.2, 2.750 g/l KCl, 185.100 g/l NaCl and 8.850 g/l acetic acid. The companion bicarbonate concentrate of Naturalyte #9006 is made by dissolving a particulate admixture of sodium bicarbonate (626 grams) and sodium chloride (221 grams) to form a bicarbonate concentrate containing 24.715 g/l NaCl and 70.006 g/l NaHCO.sub.3.
The Drake-Willock Central Delivery System 7702 comprises interconnected reciprocating proportioning pump means to admix an acid-containing concentrate and a bicarbonate-comprising concentrate with water to produce dialysate. This equipment is designed to use products such as marketed by Renal Systems, Inc. under the tradename of BC-1 SB-1000 Bicarbonate System. This bicarbonate concentrate contains 23.59 g/l NaCl and 66.03 g/l NaHCO.sub.3. For single patient use, requiring 190 liters dialysate per patient, a bicarbonate-comprising concentrate is made by dissolving the contents of the marketed BC-1 Bicarbonate Concentrate Powder containing 223 grams NaCl and 624 grams NaHCO.sub.3 in 2.5 gallons of water (9.45 liters). The companion SB-1000 aqueous acid concentrate marketed contains 3.85 g/l CaCl.sub.2, 1.42 g/l MgCl.sub.2, 2.96 g/l KCl, 91.85 g/l NaCl and 4.82 g/l acetic acid. When 9.45 liters of this acid concentrate and 9.45 liters of the aforementioned bicarbonate concentrate are proportionately admixed with 171 liters of water, 190 liters of dialysate is produced.
Recent patent art dealing with apparatus and method for preparing a hemodialysis solution, optionally containing bicarbonate, is reviewed in the aforesaid U.S. Pat. No. 4,202,760 to Storey et al issued May 13, 1980. U.S. Pat. Nos. 3,515,275 and 3,920,556 and patents cited therein describe the use of positive displacement piston pumps in continuous dialysate supply systems for a single artificial kidney. Other patents relating thereto include: U.S. Pat. Nos. 3,406,826, 3,598,727 and 3,878,095. These patents disclose double-acting piston and cylinder units or variable output positive displacement pumps which are mechanically adjustable for controllable response to measurement of conductivity or dialysate component concentrations to adjust the product solution (dialysate) concentrate to pre-set, predetermined limits. Additional patents which should be considered to place the present invention in proper perspective include U.S. Pat. Nos 3,352,779; 3,690,340, 3,722,680; 3,753,493; 3,843,099 and 3,882,020.